Human astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturation
dc.citation.articleNumber | e00802-23 | |
dc.citation.issueNumber | 8 | |
dc.citation.journalTitle | Journal of Virology | |
dc.citation.volumeNumber | 97 | |
dc.contributor.author | Ykema, Matthew | |
dc.contributor.author | Ye, Kai | |
dc.contributor.author | Xun, Meng | |
dc.contributor.author | Harper, Justin | |
dc.contributor.author | Betancourt-Solis, Miguel A. | |
dc.contributor.author | Arias, Carlos F. | |
dc.contributor.author | McNew, James A. | |
dc.contributor.author | Tao, Yizhi Jane | |
dc.date.accessioned | 2024-05-03T15:51:11Z | |
dc.date.available | 2024-05-03T15:51:11Z | |
dc.date.issued | 2023 | |
dc.description.abstract | The human astrovirus (HAstV) is a non-enveloped, single-stranded RNA virus that is a common cause of gastroenteritis. Most non-enveloped viruses use membrane disruption to deliver the viral genome into a host cell after virus uptake. The virus–host factors that allow for HAstV cell entry are currently unknown but thought to be associated with the host-protease-mediated viral maturation. Using in vitro liposome disruption analysis, we identified a trypsin-dependent lipid disruption activity in the capsid protein of HAstV serotype 8. This function was further localized to the P1 domain of the viral capsid core, which was both necessary and sufficient for membrane disruption. Site-directed mutagenesis identified a cluster of four trypsin cleavage sites necessary to retain the lipid disruption activity, which is likely attributed to a short stretch of sequence ending at arginine 313 based on mass spectrometry of liposome-associated peptides. The membrane disruption activity was conserved across several other HAstVs, including the emerging VA2 strain, and effective against a wide range of lipid identities. This work provides key functional insight into the protease maturation process essential to HAstV infectivity and presents a method to investigate membrane penetration by non-enveloped viruses in vitro. | |
dc.identifier.citation | Ykema, M., Ye, K., Xun, M., Harper, J., Betancourt-Solis, M. A., Arias, C. F., McNew, J. A., & Tao, Y. J. (2023). Human astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturation. Journal of Virology, 97(8), e00802-23. https://doi.org/10.1128/jvi.00802-23 | |
dc.identifier.digital | human-astrovirus-capsid-protein | |
dc.identifier.doi | https://doi.org/10.1128/jvi.00802-23 | |
dc.identifier.uri | https://hdl.handle.net/1911/115555 | |
dc.language.iso | eng | |
dc.publisher | American Society for Microbiology | |
dc.rights | Except where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Human astrovirus capsid protein releases a membrane lytic peptide upon trypsin maturation | |
dc.type | Journal article | |
dc.type.dcmi | Text | |
dc.type.publication | publisher version |
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